GLUCOREGULATORY PEPTIDE HORMONES

当β细胞失去它们的功能时，胰岛素抵抗个体就会成为糖尿病患者。 对葡萄糖的正常反应能力和对前 存在胰岛素抵抗。 为了确定β细胞缺陷， 结果在NIDDM中，我们计划在大鼠中表征分子， 正常β细胞代偿的代谢和生理成分 1）高血糖钳夹，2）地塞米松诱导的反应 治疗，和3）肥胖，并比较这些与β细胞的各种 不能补偿这些相同因素的大鼠模型（例如ZDF-drt大鼠， GK大鼠、Zucker fa/fa大鼠和亚糖尿病链脲佐菌素后大鼠 治疗）。 功能测量包括1）胰岛素对5， 10、20 mM葡萄糖、甘油醛和琥珀酸单甲酯定位 一个模块，2）葡萄糖转运代谢，利用， 氧化和葡糖激酶活性，以进一步定位这种阻断，3） β细胞胰岛素原、GLUT-2、葡萄糖激酶和G蛋白的定量 α mRNA以确定关键蛋白质的表达是否受损，4） 含有β-葡糖激酶的GLUT-2和葡糖激酶的百分比的形态测定分析 通过免疫细胞化学测定细胞质量，5）β-细胞体积，以确定 受损β细胞团的扩张和6）形态测定评估 线粒体的完整性。 纵向 测量将从六周前开始每周进行一次， 直到糖尿病发作后六周。 希望能找到一个 在各种糖尿病大鼠模型中， 正常代偿反应的重要组成部分 到致病位点。

Insulin resistant individuals become diabetic when beta-cells lose their normal ability to respond to glucose and to compensate for the pre- existing insulin resistance. To identify the beta-cell defect that results in NIDDM, we plan to characterize in rats the molecular, metabolic and physiologic components of the normal beta-cell compensatory response induced 1) by hyperglycemic clamping, 2) by dexamethasone treatment, and 3) by obesity and compare these with beta-cells of various rat models that cannot compensate these same factors (eg ZDF-drt rats, GK rats, Zucker fa/fa rats and rats after subdiabetic streptozotocin treatment). Functional measurement include 1) insulin responses to 5, 10, 20 mM glucose, glyceraldehyde and monomethyl succinate to localize a block, 2) measurements of glucose transport metabolism, utilization, oxidation and glucokinase activity further to localize such a block, 3) quantitation of beta-cell proinsulin, GLUT-2, glucokinase and G protein alpha mRNA to determine if expression of key proteins is impaired, 4) morphometric analysis of percent GLUT-2 and glucokinase containing beta- cell mass by immunocytochemistry, 5) beta-cell volume to determine if expansion of the beta-cell mass impaired and 6) morphometric assessment of mitochondrial integrity by electronmicroscopy. Longitudinal measurements will be made a weekly intervals from six weeks before and until six weeks after the onset of diabetes. The hope is to find a consistent difference in various diabetic rat models of seemingly crucial component of the normal compensatory response that might point to the pathogenic locus.